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1.
Head Neck ; 46(3): 528-540, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38111234

RESUMEN

BACKGROUND: We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort). METHODS: Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the YuanSuTM450 gene panel (OrigiMed, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts. RESULTS: Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A). CONCLUSION: In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.


Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/genética , Epigénesis Genética , China , Neoplasias de Cabeza y Cuello/genética , Mutación
2.
Materials (Basel) ; 15(14)2022 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-35888200

RESUMEN

In this paper, a model generation algorithm for non-equal diameter particles with a specified probability density distribution is proposed. Based on considering the randomness of the size and distribution of the particles, the compact stacking of the particles is realized by the compactness algorithm, and then the spatial distribution of the tightly compacted particles is made to meet the random distribution of the specified probability density and the specified volume fraction by the filtering algorithm. The computational efficiency and effectiveness of the algorithm are verified, and the effects of the particle size and volume fraction on the distribution are analyzed. Finally, the proposed model has been used to study the permeability of a titanium porous filter cartridge. The results show that the size and location of the particle samples that are generated by the proposed algorithm follow specified probability distributions according to the requirements, and the volume fraction can be adjusted. Compared with the traditional algorithm, the computational effort and complexity are reduced. The resultant model can be used to study the permeability of porous materials and provide modeling support for structural optimization and further simulation of porous materials.

3.
R Soc Open Sci ; 9(3): 211391, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35316948

RESUMEN

Iron phosphate (Fe-P) is a main phosphorus storage form, especially in phosphorus-polluted environments. The re-release of Fe-P is a problematic result during microalgal remediation. In this study, pre-incubated Chlorella vulgaris was cultured in a BG-11 culture medium with different amounts of Fe-P. The effects of Fe-P re-release on biomass, flocculation and removal of PO4 3- were investigated. The results indicated that C. vulgaris can promote the dissolution and release of Fe-P when the pH is 7, and the amount of Fe-P (ΔQ) released in 200 ml water reaches 0.055-0.45 mg d-1 under a C. vulgaris concentration of 5.6 × 105-8 × 105 cells ml-1. The growth of C. vulgaris was inhibited because of the flocculation behaviour of Fe3 + in the release stage, which is associated with a specific growth rate of 0.3-0.4 d-1 and a phosphorus removal rate below 30%. However, this process, in the long term, indicates a favourable transformation in which Fe-P becomes bioavailable under the action of C. vulgaris. Microalgae outbreaks may be triggered by persistent interactions between Fe-P and C. vulgaris. This study provides an important reference for the application of C. vulgaris in a Fe-P-rich environment.

4.
ISA Trans ; 128(Pt B): 136-143, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34865844

RESUMEN

By integrating the event-based mechanism and the model predictive control (MPC) method, an improved event-based MPC framework is constructed for the nonlinear control problem subject to disturbances. Firstly, a new event-triggering condition is suggested, which is constructed on the basis of the gradients of the differences between the optimal state prediction and the actual one at two consecutive sample times. Then, an event-based MPC algorithm is further proposed, in which the dual-mode control technique is incorporated to handle the nonlinear perturbed system. Furthermore, it is strictly demonstrated that the proposed algorithm will ensure the feasibility of the MPC method and the stability of the considered system, while significantly decreasing the number of solving optimization problems, based on which resources for information transfer can be effectively saved. Finally, simulations and comparisons are shown to verify the efficacy of the proposed framework.

5.
Clin Cancer Res ; 27(13): 3757-3771, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33811153

RESUMEN

PURPOSE: The limited efficacy of chimeric antigen receptor (CAR) T-cell therapies with solid malignancies prompted us to test whether epigenetic therapy could enhance the antitumor activity of B7-H3.CAR T cells with several solid cancer types. EXPERIMENTAL DESIGN: We evaluated B7-H3 expression in many human solid cancer and normal tissue samples. The efficacy of the combinatorial therapy with B7-H3.CAR T cells and the deacetylase inhibitor SAHA with several solid cancer types and the potential underlying mechanisms were characterized with in vitro and ex vivo experiments. RESULTS: B7-H3 is expressed in most of the human solid tumor samples tested, but exhibits a restricted expression in normal tissues. B7-H3.CAR T cells selectively killed B7-H3 expressing human cancer cell lines in vitro. A low dose of SAHA upregulated B7-H3 expression in several types of solid cancer cells at the transcriptional level and B7-H3.CAR expression on human transgenic T-cell membrane. In contrast, the expression of immunosuppressive molecules, such as CTLA-4 and TET2, by T cells was downregulated upon SAHA treatment. A low dose of SAHA significantly enhanced the antitumor activity of B7-H3.CAR T cells with solid cancers in vitro and ex vivo, including orthotopic patient-derived xenograft and metastatic models treated with autologous CAR T-cell infusions. CONCLUSIONS: Our results show that our novel strategy which combines SAHA and B7-H3.CAR T cells enhances their therapeutic efficacy with solid cancers and justify its translation to a clinical setting.


Asunto(s)
Antígenos B7 , Inhibidores de Histona Desacetilasas/uso terapéutico , Inmunoterapia Adoptiva , Neoplasias/terapia , Receptores Quiméricos de Antígenos/uso terapéutico , Animales , Terapia Combinada , Humanos , Ratones , Células Tumorales Cultivadas
6.
Mol Cancer Ther ; 20(3): 577-588, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33653946

RESUMEN

Radiotherapy (RT) is a key treatment for prostate cancer. However, RT resistance can contribute to treatment failure. Prostate cancer stem cells (PCSCs) are radioresistant. We recently found that fractionated irradiation (FIR) upregulates expression of the immune checkpoint B7-H3 (CD276) on PCSCs and bulk cells in each prostate cancer cell line tested. These findings prompted us to investigate whether B7-H3 targeting chimeric antigen receptor (CAR) T cells, which may abrogate function of an immune checkpoint and mediate lysis of targeted cells, can target RT-resistant PCSCs in vitro and in vivo. B7-H3 expression is naturally higher on PCSCs than bulk prostate cancer cells and cytotoxicity of B7-H3 CAR T cells to PCSCs is more potent than to bulk prostate cancer cells. Furthermore, FIR significantly upregulates B7-H3 expression on PCSCs and bulk prostate cancer cells. The duration of FIR or single-dose irradiation-induced further upregulation of B7-H3 on bulk prostate cancer cells and PCSCs lasts for up to 3 days. B7-H3 CAR T-cell cytotoxicity against FIR-resistant PCSCs at a low effector to target ratio of 1:1 was assessed by flow cytometry and sphere formation assays. Further upregulation of B7-H3 expression by FIR made PCSCs even more sensitive to B7-H3 CAR T-cell-mediated killing. Consequently, the FIR and B7-H3 CAR T-cell therapy combination is much more effective than FIR or CAR T cells alone in growth inhibition of hormone-insensitive prostate cancer xenografts in immunodeficient mice. Our work provides a sound basis for further development of this unique combinatorial model of RT and B7-H3 CAR T-cell therapy for prostate cancer. SIGNIFICANCE: We demonstrate that FIR significantly upregulates B7-H3 expression by RT-resistant PCSCs and bulk cells; cytotoxicity of B7-H3 CAR T cells to FIR-treated PCSCs is potent and results in significantly improved antitumor efficacy in mice.


Asunto(s)
Antígenos B7/metabolismo , Células Madre Neoplásicas/metabolismo , Neoplasias de la Próstata/terapia , Receptores Quiméricos de Antígenos/metabolismo , Animales , Humanos , Masculino , Ratones , Neoplasias de la Próstata/patología
7.
Stem Cell Rev Rep ; 17(3): 862-877, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33230612

RESUMEN

Tissue engineered vascular grafts (TEVGs) generated from human primary cells represent a promising vascular interventional therapy. However, generation and application of these TEVGs may be significantly hindered by the limited accessibility, finite expandability, donor-donor functional variation and immune-incompatibility of primary seed cells from donors. Alternatively, human induced pluripotent stem cells (hiPSCs) offer an infinite source to obtain functional vascular cells in large quantity and comparable quality for TEVG construction. To date, TEVGs (hiPSC-TEVGs) with significant mechanical strength and implantability have been generated using hiPSC-derived seed cells. Despite being in its incipient stage, this emerging field of hiPSC-TEVG research has achieved significant progress and presented promising future potential. Meanwhile, a series of challenges pertaining hiPSC differentiation, vascular tissue engineering technologies and future production and application await to be addressed. Herein, we have composed this review to introduce progress in TEVG generation using hiPSCs, summarize the current major challenges, and encapsulate the future directions of research on hiPSC-based TEVGs. Graphical abstract.


Asunto(s)
Células Madre Pluripotentes Inducidas , Prótesis Vascular , Humanos
8.
Bioengineered ; 11(1): 1112-1123, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33124951

RESUMEN

Recently, increasing studies suggested that lncRNA SNHG12 was aberrantly expressed in kinds of cancers. However, definite prognostic value of SNHG12 remains unclear. We conducted this meta-analysis to evaluate the association between SNHG12 expression level and cancer prognosis. A literature retrieval was conducted by searching kinds of databases. The meta-analysis was performed by using Revman 5.2 and Stata 12.0 software. Besides, The Cancer Genome Atlas dataset was analyzed to validate the results in our meta-analysis via using Gene Expression Profiling Interactive Analysis. The pooled results showed that high SNHG12 expression significantly indicated worse overall survival and recurrence-free survival. Tumor type, sample size, survival analysis method, and cutoff value did not alter SNHG12 prognosis value according to stratified analysis results. Additionally, higher expression of SNHG12 suggested unfavorable clinicopathological outcomes including larger tumor size, lymph node metastasis, distant metastasis, and advanced clinical stage. Online cross-validation in TCGA dataset further indicated that cancer patients with upregulated SNHG12 expression had worse overall survival and disease-free survival. Therefore, elevated SNHG12 expression was associated with poor survival and unfavorable clinical outcomes in various cancers, and therefore might be a potential prognostic biomarker in human cancers. Abbreviations Akt: protein kinase B; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; ceRNA: competitive endogenous RNA; CNKI: China National Knowledge Infrastructure; CI: confidence interval; CCNE1: cyclin E1; COAD: colon adenocarcinoma; DM: distant metastasis; DFS: disease-free survival; EMT: epithelial-mesenchymal transition; FISH: fluorescence in situ hybridization; FIGO: the International Federation of Gynecology and Obstetrics; GEPIA: Gene Expression Profiling Interactive Analysis; HR: hazard ratio; HIFα: hypoxia-inducible factor 1 α; KIRC: kidney renal clear cell carcinoma; KIRP: kidney renal papillary cell carcinoma; LIHC: hepatocellular carcinoma; LNM: lymph node metastasis; mTOR: mechanistic target of rapamycin kinase; MMP-9: matrix metalloproteinase 9; MCL1: myeloid cell leukemia 1; MLK3: mixed-lineage protein kinase 3; N/A: not available; NOS: Newcastle-Ottawa Scale; OR: odd ratio; OS: overall survival; PSA: prostate-specific antigen; PI3K: phosphoinositide 3-kinase; qRT-PCR: quantitative real-time polymerase chain reaction; READ: rectum adenocarcinoma; RFS: recurrence-free survival; SARC: sarcoma; SNHG12: small nucleolar RNA host gene 12; STAT3: signal transducer and activator of transcription 3; SOX4: SRY-box transcription factor 4; SOX5: SRY-box transcription factor 5; STAD: stomach adenocarcinoma; TCGA: The Cancer Genome Atlas; TNM: tumor node metastasis; WWP1: WW domain-containing E3 ubiquitin protein ligase 1; WHO grade: World Health Organization grade; ZEB2: zinc finger E-box-binding homeobox 2.


Asunto(s)
ARN Largo no Codificante/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , ARN Largo no Codificante/genética , Sarcoma/genética , Sarcoma/metabolismo , Sarcoma/patología , Programas Informáticos
9.
Front Cell Dev Biol ; 8: 870, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32984346

RESUMEN

RNA modifications have emerged as key regulators of transcript expression in diverse physiological and pathological processes. As one of the most prevalent types of RNA modifications, N6-methyladenosine (m6A) has become the highlight in modulation of various diseases through interfering RNA splicing, translation, nuclear export, and decay. In many cases, the detailed functions of m6A in cellular processes and diseases remain unclear. Notably, recent studies have determined the relationship between m6A modification and musculoskeletal disorders containing osteosarcoma, osteoarthritis, rheumatoid arthritis, osteoporosis, etc. Herein, this review comprehensively summarizes the recent advances of m6A modification in pathogenesis and progression of musculoskeletal diseases. Specifically, the underlying molecular mechanisms, detection technologies, regulatory functions, clinical implications, and future perspectives of m6A in musculoskeletal disorders are discussed, with the aim to provide a novel insight into their association.

10.
11.
Cell Commun Signal ; 18(1): 36, 2020 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-32138738

RESUMEN

BACKGROUND: The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response. METHODS: High aldehyde dehydrogenase activity (ALDH)bright and CD44+/CD24-/ESA+ cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The results indicate that DSF/Cu induced a similar extent of IDC in both BCSCs and non-BCSCs and rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. IR and DSF/Cu induced ICD of BCSCs could be partly reversed by pre-treatment of BCSCs with a reactive oxygen species (ROS) scavenger and XBP1s inhibitors. CONCLUSION: DSF/Cu rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. Our data demonstrate the potential of IR and DSF/Cu to induce ICD in BCSCs and non-BCSCs leading to robust immune responses against not only differentiated/differentiating breast cancer cells but also BCSCs, the root cause of cancer formation, progression and metastasis.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama/tratamiento farmacológico , Disulfiram , Reposicionamiento de Medicamentos , Muerte Celular Inmunogénica/efectos de los fármacos , Tolerancia a Radiación/efectos de los fármacos , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Línea Celular Tumoral , Disulfiram/administración & dosificación , Disulfiram/farmacología , Femenino , Humanos , Células Madre Neoplásicas
12.
Front Mol Biosci ; 6: 134, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31850367

RESUMEN

Chondrosarcoma is the second most common malignant bone tumor. Current therapies remain ineffective, resulting in poor prognoses. Biomarkers for chondrosarcoma and predictors of its prognosis have not been established. Mental health-related proteins have been associated with the pathogenesis, progression, and prognosis of many cancers, but their association with chondrosarcoma has not been reported. In this study, the expression and clinicopathological significance of the mental health-related proteins DAXX, DRD3, and DISC1 in chondrosarcoma tissue samples were examined, over an 84-months follow-up period. In immunohistochemical analysis, the rates of positive DAXX, DRD3, and DISC1 expression were significantly higher in chondrosarcoma than in osteochondroma tissue (P < 0.01). The percentages of positive DAXX, DRD3, and DISC1 expression were significantly lower in tissues with good differentiation (P < 0.01), AJCC stage I/ II (P < 0.01), Enneking stage I (P < 0.01), and non-metastasis (P < 0.05), respectively. In Kaplan-Meier survival analysis, significantly shorter mean survival times were associated with moderate and poor differentiation (P = 0.000), AJCC stage III/IV (P = 0.000), Enneking stage II/III (P = 0.000), metastasis (P = 0.019), invasion (P = 0.013), and positive DAXX (P = 0.012), and/or DRD3 (P = 0.018) expression. In Cox regression analysis, moderate and poor differentiation (P = 0.006), AJCC stage III/IV (P = 0.013), Enneking stage II/III (P = 0.016), metastasis (P = 0.033), invasion (P = 0.011), and positive DAXX (P = 0.033), and/or DRD3 (P = 0.025) staining correlated negatively with the postoperative survival rate and positively with mortality. In competing-risks regression analysis, differentiation (P = 0.005), metastasis (P = 0.014), invasion (P = 0.028), AJCC stage (P = 0.003), Enneking stage (P = 0.036), and DAXX (P = 0.039), and DRD3(P = 0.019) expression were independent predictors of death from chondrosarcoma. The areas under receiver operating characteristic curves for DAXX, DRD3, and DISC1 expression were 0.673 (95% CI, 0.557-0.788; P = 0.010), 0.670 (95% CI, 0.556-0.784; P = 0.011), and 0.688 (95% CI, 0.573-0.802; P = 0.005), respectively. These results suggest that DAXX, DRD3, and DISC1 could serve as biomarkers of chondrosarcoma progression and predictors of its prognosis.

13.
Onco Targets Ther ; 12: 8411-8420, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31695419

RESUMEN

AIMS: Chondrosarcoma (CS) is a high-morbidity, relatively common bone malignancy without well-established biomarkers. The proteins EAAT1, DHFR, and fetuin-A have been investigated in many cancers, but their specific relationship to CS has not been reported. The present study examined EAAT1, DHFR, and fetuin-A expression in CS and the clinicopathological significance of these proteins in CS pathogenesis, progression, and prognosis. METHODS: EAAT1, DHFR, and fetuin-A protein levels in 80 CS and 25 chondroma specimens were measured by immunohistochemistry and related to histological and clinical factors with chi-squared tests. Following univariate survival analysis, ROC curves calculation, and multivariate analysis. RESULTS: EAAT1, DHFR, and fetuin-A expression levels were significantly higher in the CS group than in the chondroma group (p < 0.05). Their immunopositivity rates were significantly greater in tissues with moderate or poor tumor differentiation, AJCC stage III or IV, Enneking stage II or III, and metastasis (p<0.05 or p<0.01 or p<0.001). Kaplan-Meier survival analysis showed significantly shorter survival in patients with moderately or poorly differentiated tumors, AJCC stage III or IV CS, Enneking stage II or III CS, metastasis, invasion, or EAAT1, DHFR, and fetuin-A immunopositivity (p < 0.05 or p < 0.001). Cox regression analysis showed that moderate or poor tumor differentiation, AJCC stage III or IV, Enneking stage II or III, metastasis, invasion, and EAAT1, DHFR, or fetuin-A immunopositivity correlated negatively with postoperative survival and positively with mortality (p < 0.05). The AUCs for EAAT1, DHFR, and fetuin-A were 0.654 (95% CI: 0.532-0.776, p = 0.025), 0.638 (95% CI: 0.519-0.756, p = 0.039), and 0.670 (95% CI: 0.556-0.784, p = 0.011), respectively. CONCLUSION: EAAT1, DHFR, and fetuin-A may be important biomarkers of the pathogenesis and progression of CS and predictors of its prognosis.

14.
Pathol Res Pract ; 215(6): 152420, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31060912

RESUMEN

Most bone cancers have a high risk of metastasis, recurrence, and poor prognosis. Although conventional treatments are still the most important therapy, disadvantages still exist. Therefore, there is an unmet need to develop effective strategies. Immunotherapy is a promising therapy. Immunotherapies targeting checkpoints have proven to be successful, but B7-H3 (CD276, clusters of differentiation protein 276), a member of the B7-family of co-stimulatory molecules, is not being widely studied in bone cancers. This review summarized the studies on B7-H3 in bone cancers. 4 studies investigated B7-H3 expression in osteosarcoma, but there is no study on B7-H3 expression in chondrosarcoma. Two studies investigated the possibility to treat Ewing`s sarcoma through targeting the B7-H3 CAR (chimeric antigen receptors) T-cells or using anti-B7-H3 antibody. A study observed the growth of myeloma in B7-H3-deficient mice and the therapeutic effect of B7-H3 antibody and a study invested B7-H3 expression in myeloma patients. One study reported B7-H3 expression in osteoclastomas and one study investigated B7-H3 expression in chordoma tumor tissues. Two clinical trials are conducting on the therapy of osteosarcoma and myeloma using B7-H3 as a target. In conclusion, B7-H3 could be a target of bone cancers.


Asunto(s)
Antígenos B7 , Neoplasias Óseas , Animales , Antígenos B7/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Humanos , Inmunoterapia/métodos , Ratones
15.
Clin Cancer Res ; 25(12): 3673-3688, 2019 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-30885939

RESUMEN

PURPOSE: The overall biological roles and clinical significance of most long noncoding RNAs (lncRNA) in chemosensitivity are not fully understood. We investigated the biological function, mechanism, and clinical significance of lncRNA NR_034085, which we termed miRNA processing-related lncRNA (MPRL), in tongue squamous cell carcinoma (TSCC). EXPERIMENTAL DESIGN: LncRNA expression in TSCC cell lines with cisplatin treatment was measured by lncRNA microarray and confirmed in TSCC tissues. The functional roles of MPRL were demonstrated by a series of in vitro and in vivo experiments. The miRNA profiles, RNA pull-down, RNA immunoprecipitation, serial deletion analysis, and luciferase analyses were used to investigate the potential mechanisms of MPRL. RESULTS: We found that MPRL expression was significantly upregulated in TSCC cell lines treated with cisplatin and transactivated by E2F1. MPRL controlled mitochondrial fission and cisplatin sensitivity through miR-483-5p. In exploring the underlying interaction between MPRL and miR-483-5p, we identified that cytoplasmic MPRL directly binds to pre-miR-483 within the loop region and blocks pre-miR-483 recognition and cleavage by TRBP-DICER-complex, thereby inhibiting miR-483-5p generation and upregulating miR-483-5p downstream target-FIS1 expression. Furthermore, overexpression or knockdown MPRL altered tumor apoptosis and growth in mouse xenografts. Importantly, we found that high expression of MPRL and pre-miR-483, and low expression of miR-483-5p were significantly associated with neoadjuvant chemosensitivity and better TSCC patients' prognosis. CONCLUSIONS: We propose a model in which lncRNAs impair microprocessor recognition and are efficient of pre-miRNA cropping. In addition, our study reveals a novel regulatory network for mitochondrial fission and chemosensitivity and new biomarkers for prediction of neoadjuvant chemosensitivity in TSCC.These findings uncover a novel mechanism by which lncRNA determines mitochondrial fission and cisplatin chemosensitivity by inhibition of pre-miRNA processing and provide for the first time the rationale for lncRNA and miRNA biogenesis for predicting chemosensitivity and patient clinical prognosis.


Asunto(s)
Cisplatino/farmacología , MicroARNs/genética , Dinámicas Mitocondriales/genética , ARN Largo no Codificante/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/genética , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Resistencia a Antineoplásicos , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de la Lengua/patología
16.
Cancer Res ; 79(6): 1069-1084, 2019 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-30659020

RESUMEN

miRNAs that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNAs (mitomiR). mitomiRs have been shown to modulate the translational activity of the mitochondrial genome, yet their role in mitochondrial DNA (mtDNA) transcription remains to be determined. Here we report that the mitomiR-2392 regulates chemoresistance in tongue squamous cell carcinoma (TSCC) cells by reprogramming metabolism via downregulation of oxidative phosphorylation and upregulation of glycolysis. These effects were mediated through partial inhibition of mtDNA transcription by mitomiR-2392 rather than through translational regulation. This repression required specific miRNA-mtDNA base pairing and Argonaute 2. mitomiR-2392 recognized target sequences in the H-strand and partially inhibited polycistronic mtDNA transcription in a cell-specific manner. A retrospective analysis of TSCC patient tumors revealed a significant association of miR-2392 and regulated mitochondrial gene expression with chemosensitivity and overall survival. The clinical relevance of targeted mitochondrial genes was consistently validated by The Cancer Genome Atlas RNA sequencing in multiple types of cancer. Our study revealed for the first time the role of mitomiR in mtDNA transcription and its contribution to the molecular basis of tumor cell metabolism and chemoresistance.Significance: These findings uncover a novel mechanism by which mitomiRNA regulates mitochondrial transcription and provide rationale for use of mitomiRNA and mtDNA-encoded genes to predict chemosensitivity and patient clinical prognosis.


Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/farmacología , ADN Mitocondrial/metabolismo , Resistencia a Antineoplásicos/genética , MicroARNs/metabolismo , Mitocondrias/genética , Neoplasias de la Lengua/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Apoptosis , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Biomarcadores de Tumor , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Núcleo Celular/genética , Núcleo Celular/metabolismo , Proliferación Celular , Reprogramación Celular , ADN Mitocondrial/genética , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Genoma Mitocondrial , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Mitocondrias/metabolismo , Fosforilación Oxidativa , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias de la Lengua/genética , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/patología , Transcripción Genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Head Neck ; 41(5): 1359-1366, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30561069

RESUMEN

BACKGROUND: Reconstruction of hemiglossectomy defects requires careful flap design to avoid adverse functional and aesthetic outcomes. METHODS: Hemitongue specimens were obtained from minipigs to study the three-dimensional anatomy and to define anatomic landmarks for precise measurements of flap requirement. The concept developed in animal models was then applied to hemiglossectomy reconstruction in clinical practice. Sixty-one patients were randomly enrolled into the following two groups: a "five-point eight-line segment" (FIPELS) flap design group (28 patients) and a conventional group (33 patients). Functional and aesthetic outcomes were compared between the two groups. RESULTS: All flaps designed with the FIPELS technique matched the hemiglossectomy defects without the need for flap trimming, thus reducing the operating time (P = .03). Swallowing functions, speech intelligibility, and aesthetic outcomes were superior in the FIPELS group than that in the conventional group (P < .05). CONCLUSIONS: The FIPELS flap design for hemiglossectomy reconstruction yields improved functional and aesthetic outcomes compared to a conventional flap design.


Asunto(s)
Colgajos Tisulares Libres/trasplante , Glosectomía/métodos , Imagenología Tridimensional , Procedimientos de Cirugía Plástica/métodos , Calidad de Vida , Neoplasias de la Lengua/cirugía , Adulto , Anciano , Animales , China , Estudios de Cohortes , Deglución/fisiología , Modelos Animales de Enfermedad , Femenino , Antebrazo/cirugía , Colgajos Tisulares Libres/irrigación sanguínea , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Inteligibilidad del Habla , Porcinos , Porcinos Enanos , Muslo/cirugía , Neoplasias de la Lengua/patología
18.
Artículo en Inglés | MEDLINE | ID: mdl-27391313

RESUMEN

Hilarionite (Fe2 (SO4)(AsO4)(OH)·6H2O) is a new Fe sulphoarsenates mineral, which recently is found in the famous Lavrion ore district, Atliki Prefecture, Greece. The spectroscopic study of hilarionite enriches the data of arsenic mineralogy in supergene environment of a mine area. The infrared and Raman means are used to characterize the molecular structure of this mineral. The IR bands at 875 and 905cm(-1) are assigned to the antisymmetric stretching vibrations of AsO4(3-). The IR bands at 1021, 1086 and 1136cm(-1) correspond to the possible antisymmetric and symmetric stretching vibrations of SO4(2-). The Raman bands at 807, 843 and 875cm(-1) clearly show that arsenate components in the mineral structure, which are assigned to the symmetric stretching vibrations (ν1) of AsO4(3-) (807 and 843cm(-1)) and the antisymmetric vibration (ν3) (875cm(-1)). IR bands provide more sulfate information than Raman, which can be used as the basis to distinguish hilarionite from kankite. The powder XRD data shows that hilarionite has obvious differences with the mineral structure of kankite. The thermoanalysis and SEM-EDX results show that hilarionite has more sulfate than arsenate.

19.
Pathol Res Pract ; 212(7): 636-42, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27155928

RESUMEN

OBJECTIVE: This study investigated the protein expression and clinicopathological significance of Thy1 and CD49f in chondrosarcomas. METHODS: Thy1 and CD49f protein expression in 59 chondrosarcomas and 33 osteochondromas were measured by immunohistochemical staining. RESULTS: The percentage of positive Thy1 and CD49f expression was significantly higher in patients with chondrosarcoma than in patients with osteochondroma (P<0.01). The percentage of positive Thy1 and CD49f expression was significantly lower in patients with histological grade I, Enneking stage I, AJCC stage I/II stage, non-metastatic and non-invasive chondrosarcoma than in patients with histological grade III, Enneking stage II+III, AJCC stage III/IV, metastatic and invasive chondrosarcoma (P<0.05 or P<0.01). Thy1 expression was positively correlated with CD49f expression in chondrosarcoma. Kaplan-Meier survival analysis showed that histological grade, AJCC stage, Enneking stage, metastasis, invasion, and Thy1 and CD49f expression significantly correlated with shorter mean survival time in chondrosarcoma patients (P<0.05 or P<0.01). Cox multivariate analysis showed that positive Thy1 and CD49f expression was an independent prognostic factor that negatively correlated with overall postoperative survival. CONCLUSION: Positive Thy1 and CD49f expression is significantly associated with the progression and poor prognosis of chondrosarcoma.


Asunto(s)
Neoplasias Óseas/metabolismo , Condrosarcoma/metabolismo , Integrina alfa6/metabolismo , Osteocondroma/metabolismo , Antígenos Thy-1/metabolismo , Adulto , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Condrosarcoma/mortalidad , Condrosarcoma/patología , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Osteocondroma/mortalidad , Osteocondroma/patología , Pronóstico , Tasa de Supervivencia
20.
Chemosphere ; 153: 146-54, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27016809

RESUMEN

Although the removal of arsenic(V) (As(V)) from solution can be improved by forming metal-bearing coatings on solid media, there has been no research to date examining the relationship between the coating and As(V) sorption performance. Manganese-coated bone char samples with varying concentrations of Mn were created to investigate the adsorption and desorption of As(V) using batch and column experiments. Breakthrough curves were obtained by fitting the Convection-Diffusion Equation (CDE), and retardation factors were used to quantify the effects of the Mn coatings on the retention of As(V). Uncoated bone char has a higher retention factor (44.7) than bone char with 0.465 mg/g of Mn (22.0), but bone char samples with between 5.02 mg/g and 14.5 mg/g Mn have significantly higher retention factors (56.8-246). The relationship between retardation factor (Y) and Mn concentration (X) is Y = 15.1 X + 19.8. Between 0.2% and 0.6% of the sorbed As is desorbed from the Mn-coated bone char at an initial pH value of 4, compared to 30% from the uncoated bone char. The ability of the Mn-coated bone char to neutralize solutions increases with increased amounts of Mn on the char. The results suggest that using Mn-coated bone char in Permeable Reactive Barriers would be an effective method for remediating As(V)-bearing solutions such as acid mine drainage.


Asunto(s)
Arsénico/química , Carbón Orgánico/química , Restauración y Remediación Ambiental/métodos , Manganeso/química , Nanopartículas del Metal/química , Contaminantes Químicos del Agua/química , Adsorción , Huesos , Soluciones
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